Proteomic Signature of Urosepsis: From Discovery in a Rabbit Model to Validation in Humans

Urosepsis
after upper urinary tract endoscopic lithotripsy (UUTEL)
may cause uroseptic shock with high mortality, which can be prevented
if early diagnosis and timely intervention are implemented with help
of a diagnostic protein panel. The plasma of five rabbits of uroseptic
shock and five controls was subjected to exploratory proteomics to
search biomarker candidates from proteomic profiles related to uroseptic
shock. Then, plasma from 21 nonsepsis and 20 urosepsis patients according
to European diagnostic criteria of sepsis was enrolled in the validation
study via targeted proteomics. Changes in a massive number of plasma
proteins, mainly enriched in immune regulation, coagulation, structural
repair, and transport activity, were observed in the rabbit model
of septic shock. Fifteen proteins were identified as differential
expression proteins between sepsis and nonsepsis patients. A diagnostic
model composed of three proteins lipopolysaccharide-binding protein
(LBP), clusterin (CLU), and vascular cell adhesion protein 1 (VCAM1)
was developed for the early detection (2 hours postoperatively) of
urosepsis after UUTEL, with a high area under the receiver operating
characteristic (ROC) curve of 0.921. In conclusion, changes in the
proteomic profile may reflect the underlying biological mechanisms
during the development of urosepsis and produce diagnostic biomarkers
for the early detection of urosepsis after UUTEL.